A rationalist’s guide to psychoactive drugs

This is a first draft. Over the next few days I’ll add cita­tions and that sort of thing, but I’m post­ing it as-is in or­der to so­licit feed­back. Also, I wasn’t able to find any spe­cific policy re­gard­ing men­tion of illicit sub­stances, so I’m go­ing to as­sume this is okay, but if not please let me know.

Dis­claimer: This is a work of post­mod­ern fic­tion about two ir­re­deemable junkies named Alice and Bob and their cat Fido. The views con­tained herein are not med­i­cal or le­gal ad­vice, they are not my views, and they are not the views of LessWrong.com or any of its mem­bers. In fact they are not views at all: they are transnar­ra­tive flows in al­ter­ity-space, or that’s what my lit prof tells me. I do not con­done any ille­gal ac­tivity what­so­ever, ex­cept jay­walk­ing.

Introduction

To­day, says Alice, I’m go­ing to talk to you about drugs. I’ll be cov­er­ing sev­eral nu­tri­tional sup­ple­ments, some stim­u­lants and nootrop­ics, and—as some of you have prob­a­bly guessed—I’ll also be talk­ing briefly about recre­ational drugs, par­tic­u­larly psychedelics. Now, I don’t have any sense of what the pop­u­lar per­cep­tion is of drugs around here, but I pre­sume that at least some of you will be a lit­tle put off at the sug­ges­tion of recre­ational drug use. If that is how you feel, please bear with me. To par­take or not par­take of pro­hibited sub­stances is a choice that must be made in­di­vi­d­u­ally, and for many the pay­offs may not be worth the risks; but I hope to con­vince you that, at least for some peo­ple, re­spon­si­ble drug use is a very rea­son­able and benefi­cial ac­tivity.

Well, hold on, says Bob—who takes a per­mis­sive but de­tached view of these things—hold on, now. It may be true (as cur­sory re­search will show) that drug use is far less dan­ger­ous than it’s made out to be, and it may be true that some peo­ple get a lot of en­joy­ment out of them. But if you value knowl­edge and rea­son over he­do­nic plea­sure, it seems bet­ter to cut them out en­tirely. After all, it’s your brain on the line if any­thing goes wrong!

As a mat­ter of fact, says Alice, drugs are good for more than just he­do­nism. First of all, they give you a han­dle on your own neu­ro­chem­istry. It’s un­likely that your brain is op­ti­mally tuned for the things you want to ac­com­plish, so if you can tweak it the right way, you might be able to im­prove your func­tion­ing. In ex­treme cases, you might have chronic im­bal­ances lead­ing to de­pres­sion, ma­nia, etc., in which case you’ll prob­a­bly want to talk to a doc­tor about med­i­ca­tion; but the abil­ity to use drugs to change your­self goes well be­yond this. For ex­am­ple, ju­di­cious use of MDMA can help you re­train your so­cial re­flexes and be­come more out­go­ing and so­cia­ble. Hav­ing this han­dle also al­lows you to be­gin to ex­per­i­men­tally cor­re­late your sub­jec­tive ex­pe­rience with the phys­i­cal pro­cesses to which they cor­re­spond, and by care­fully ob­serv­ing more un­usual states of con­scious­ness, you broaden your un­der­stand­ing of the mind and how it op­er­ates. Lastly, psychedelics can some­times help you un­der­stand things differ­ently or more deeply. I’ve of­ten found my math­e­mat­i­cal abil­ity im­proved by mod­er­ate doses of LSD, for ex­am­ple. So, even for some­one con­cerned pri­mar­ily with ra­tio­nal­ity and the ac­cu­mu­la­tion and ap­pli­ca­tion of knowl­edge, drugs are at least worth con­sid­er­ing.

And what of the risks? says Bob.

I was get­ting to that, says Alice. There will always be a risk/​benefit trade­off, but the risks can be min­i­mized through care­ful and re­spon­si­ble use:

  • Thor­oughly re­search ev­ery new drug be­fore try­ing it. Un­for­tu­nately, in the case of pro­hibited sub­stances, very lit­tle good clini­cal re­search has been done (this has started to change in re­cent years, but there are still vast swaths of un­charted ter­ri­tory). Nev­er­the­less, there’s good in­for­ma­tion to be had. For drugs used recre­ation­ally, I usu­ally start at Erowid.org, which pro­vides an over­all sum­mary of the effects of a wide va­ri­ety of drugs; aca­demic cita­tions and some­times full ar­ti­cles, if there are any; “trip re­ports” (anec­do­tal ev­i­dence is bet­ter than noth­ing, es­pe­cially if there’s a lot of it); and other use­ful in­for­ma­tion. For nootrop­ics and “smart drugs”, I usu­ally just start with a Google search and/​or Wikipe­dia.

  • Pay par­tic­u­lar at­ten­tion to ad­dic­tive po­ten­tial, tox­i­c­ity and con­traindi­ca­tions. Drugs with high ad­dic­tive po­ten­tial re­quire ex­tra cau­tion, and should per­haps be avoided by peo­ple with akra­sia prob­lems. Also be mind­ful of any his­tory of ad­dic­tion you may have in your fam­ily. Re­gard­ing con­traindi­ca­tions: beside drug in­ter­ac­tions, a lot of this is just com­mon sense. If you are prone to anx­iety, you should prob­a­bly avoid am­phetamines. As far as tox­i­c­ity goes, a good num­ber to look at is the ther­a­peu­tic in­dex, which is the ra­tio of the LD50 (the dose, per kilo­gram of body weight, at which 50% of ex­per­i­men­tal test sub­jects (usu­ally ro­dents) die) to the effec­tive dose (per kilo­gram of body weight). How­ever, keep in mind also that fre­quent or heavy drug use can tax the liver, and that oth­er­wise safe chem­i­cals may build up to toxic lev­els over time.

  • If you de­cide to take a drug known to be ad­dic­tive, take it in mod­er­ate quan­tities over brief pe­ri­ods of time, well-sep­a­rated from each other. This is not a hard and fast rule: un­der a doc­tor’s su­per­vi­sion, for ex­am­ple, you may choose to take pre­scribed med­i­ca­tion ev­ery day. You should rec­og­nize, how­ever, that this comes at a cost: an­tide­pres­sants can be used to pull your life to­gether and over­come de­pres­sion, but it’s go­ing to be nasty com­ing off them. Fi­nally, as a rule of thumb, oral in­ges­tion is sig­nifi­cantly less ad­dic­tive than smok­ing, in­suffla­tion or in­jec­tion, since this gives a grad­ual and de­layed on­set of the re­ward stim­u­lus. For the same rea­son, you can fur­ther re­duce your chances of be­com­ing ad­dicted by tak­ing pro­drugs wher­ever pos­si­ble (e.g. Vy­vanse in­stead of Dexedrine).

  • Always take a low dose first, in case you re­act badly, and do so around other peo­ple who know what you are tak­ing.

  • To the great­est ex­tent pos­si­ble, main­tain an open and hon­est re­la­tion­ship with your doc­tor, who is in a po­si­tion to help you min­i­mize the health risks as­so­ci­ated with your drug-tak­ing.

  • If you de­cide to seek out pro­hibited sub­stances, it’s im­por­tant to have a good source of high-qual­ity product. Street drugs may be cut with cheap sub­sti­tutes or con­tam­i­nated with solvents used in ex­trac­tion/​syn­the­sis, or they may sim­ply not be what they are claimed to be. Go to peo­ple you trust who already do drugs on a reg­u­lar ba­sis, and ask them for help find­ing a rep­utable dealer.

With that out of the way, con­tinues Alice, let’s start sim­ple: what is a drug? For our pur­poses, we’ll say a drug is any sub­stance con­sumed for rea­sons other than its nu­tri­tive value or the sen­sory ex­pe­rience of con­sump­tion. We’ll speci­fi­cally be fo­cus­ing on psy­choac­tive drugs, which are con­sumed for their effects on the mind. Note that just about any­thing you eat or drink is po­ten­tially a psy­choac­tive drug, and you may not have to turn to out­landish syn­thetic com­pounds to al­ter your neu­ro­chem­istry. For ex­am­ple: af­ter three years of veg­e­tar­i­anism, I grad­u­ally be­gan to de­velop chronic anx­iety, with oc­ca­sional panic at­tacks. It plateaued at a (barely) man­age­able level, so I never ended up seek­ing med­i­cal help; it took two years be­fore I thought to try eat­ing meat again. When I fi­nally did, the anx­iety im­me­di­ately van­ished and has not re­turned. So, for me, meat is a psy­choac­tive drug. In fact, let’s talk about nu­tri­tional sup­ple­ments first.

Sup­ple­ments and Neurotransmitters

The first group of drugs we’re go­ing to be look­ing at are neu­ro­trans­mit­ters, and their chem­i­cal pre­cur­sors, which can be found at health food stores. First, there are 5-HTP and tryp­to­phan, which are sero­tonin pre­cur­sors. There is some ev­i­dence that these can help treat de­pres­sion, im­prove qual­ity of sleep, and im­prove your mood, but since you need to take it for a few days be­fore you start to no­tice the effect, it might be hard to tell if this is ac­tu­ally do­ing any­thing for you.

Next, con­sider pheny­lala­nine, an amino acid which serves as a pre­cur­sor to dopamine, nore­pinephrine and adrenal­ine. Pheny­lala­nine is first me­tab­o­lized into ty­ro­sine, which is also available as a dietary sup­ple­ment. Re­search seems to sug­gest that these are mainly effec­tive only for peo­ple un­der con­di­tions of phys­i­cal, emo­tional or men­tal stress, and don’t do much for the gen­eral pop­u­la­tion. I’ve found that, in fact, L-pheny­lala­nine has a no­tice­able up­lift­ing effect on my mood within a short time of tak­ing it; but maybe this just says some­thing about how much stress I’m un­der.

Lastly, there’s GABA, a neu­ro­trans­mit­ter which has an in­hibitory effect on the dopamine sys­tem and cer­tain other neu­ro­trans­mit­ters. In short, this will calm you down right quick, which makes it use­ful for deal­ing with in­tense and un­con­trol­lable emo­tions—anx­iety, grief, rage, etc. I find that, for this pur­pose, thea­nine is even bet­ter: it pro­motes GABA pro­duc­tion and alpha brain­wave ac­tivity, and also seems to in­crease dopamine lev­els. Its calming effect is very similar to that of GABA, but I find it much less likely to leave me feel­ing tired and out of it: if any­thing, it seems to have a mildly stim­u­lat­ing effect. As an added bonus, thea­nine ap­pears to boost the im­mune sys­tem. Thea­nine syn­er­gizes well with caf­feine, which we’ll cover shortly.

All of the above − 5-HTP, tryp­to­phan, pheny­lala­nine, ty­ro­sine, thea­nine and GABA—are not only use­ful for reg­u­lat­ing your mood, but also for learn­ing what your neu­ro­chem­istry feels like from the in­side. I found it ed­ify­ing to take fairly large doses of 5-HTP (or pheny­lala­nine, etc.) ev­ery day for a cou­ple weeks, stop for a few weeks, go back on for a cou­ple weeks, stop, etc. - all the while not­ing changes in my mood and per­cep­tion. In that re­spect, mela­tonin tablets can be added to this list: they’re not re­ally go­ing to make you a more effec­tive ra­tio­nal­ist, but they will teach you what mela­tonin does to your cog­ni­tion. Me­la­tonin will also be use­ful if you’re tak­ing stim­u­lants, which might oth­er­wise in­terfere with your sleep pat­terns.

It is also worth men­tion­ing that vi­tamin defi­cien­cies (or ex­cesses) can have a sig­nifi­cant im­pact on mood and cog­ni­tive func­tion­ing. I recom­mend tak­ing mul­ti­vi­tam­ins; this need not be a daily reg­i­men if you have a healthy diet, just kind of take them when you re­mem­ber to. Women should look for mul­ti­vi­tam­ins with iron, and men should look for those with­out.

Stimulants

Next, let’s talk about stim­u­lants, start­ing with caf­feine—by far the most pop­u­lar, al­though by no means the most effec­tive. Caf­feine works by block­ing the ac­tivity of adeno­sine, an in­hibitory neu­ro­trans­mit­ter that plays a role in sleep and drowsi­ness. As a re­sult, neu­ral ac­tivity goes up, ac­com­panied by a kick to the sym­pa­thetic ner­vous sys­tem and an in­crease in blood sugar lev­els. Taken on a fairly reg­u­lar daily sched­ule, caf­feine seems to im­prove my at­ten­tion, mo­ti­va­tion and en­ergy level. In the long term, there ap­pear to be health benefits from drink­ing coffee in this way: in ad­di­tion to its stim­u­lat­ing effects, it ap­pears to help pre­vent heart dis­ease, Alzheimer’s dis­ease and Park­in­son’s dis­ease, among oth­ers. For all-nighters, though, caf­feine is an in­fe­rior choice: al­though it suffices to keep you up and run­ning, it doesn’t seem to do much to miti­gate the cog­ni­tive effects of sleep de­pri­va­tion. Also, as in­creas­ing amounts are con­sumed, a va­ri­ety of un­pleas­ant side-effects be­gin to ap­pear, in­clud­ing tremors, heart palpi­ta­tions, anx­iety, di­ar­rhea, and de­hy­dra­tion. It should also be noted that caf­feine builds tol­er­ance, and the with­drawal is rather un­pleas­ant. De­spite this, it seems to make sense to take coffee ev­ery day in mod­er­a­tion, un­less you are es­pe­cially sen­si­tive to its nega­tive effects.

Caf­feine can also be had in tea (green tea, in par­tic­u­lar, also con­tains thea­nine, as we dis­cussed), in choco­late, prefer­ably dark (choco­late also con­tains a num­ber of other psy­choac­tive alkaloids, in­clud­ing pheny­lala­nine and theo­bromine), in caf­feine pills and in en­ergy drinks. It is per­haps worth men­tion­ing that I find that the en­ergy drinks and en­ergy shots con­tain­ing other medici­nal in­gre­di­ents (pheny­lala­nine, tau­rine, B vi­tam­ins, etc.) re­ally do seem to be slightly bet­ter, min­i­miz­ing the un­pleas­ant side effects and smooth­ing out the crash. Still, I try to avoid these be­cause of the sugar and/​or ar­tifi­cial sweet­ener con­tent. It is un­clear ex­actly what effect each of these other medici­nal in­gre­di­ents has in­di­vi­d­u­ally, if any at all, so you should also be warned that you are prob­a­bly buy­ing some non­sense along with your ac­tu­ally mind-al­ter­ing com­pounds.

Next are am­phetamines, which act on the sero­tonin, nore­pinephrine and es­pe­cially dopamine sys­tems, caus­ing in­creased fo­cus, im­proved cog­ni­tive abil­ity, and ele­vated en­ergy lev­els. They also miti­gate some of the effects of sleep de­pri­va­tion, al­though your cog­ni­tive perfor­mance will still suffer. While am­phetamines can greatly im­prove your pro­duc­tivity if used cor­rectly, they can also eas­ily do the op­po­site, be­cause it’s just as easy to hy­per­fo­cus on video games as it is to hy­per­fo­cus on neu­ral net­work al­gorithms. Body tics and bad habits can also get strongly re­in­forced, since your re­ward sys­tems are get­ting pum­mel­led by dopamine. Ba­si­cally, if you’re do­ing am­phetamines, keep your akra­sia-fight­ing sys­tems on high alert (for­tu­nately this, too, will be aided by the am­phetamines). Another down­side to am­phetamines is that they’re quite ad­dic­tive; take them ei­ther in fixed quan­tities on a reg­u­lar sched­ule (if you have a pre­scrip­tion) or else in oc­ca­sional bursts of no more than a few days, and in mod­er­ate quan­tities.

Beside ad­dic­tion, a lot of the dan­ger from am­phetamines comes from failing to eat and sleep, if you’re tak­ing them for more than a day or two. Am­phetamines are strong ap­petite sup­pres­sants, and of course they keep you awake, so you’ll need to force your­self to eat three square meals a day and get to sleep at a rea­son­able hour. Sleep is es­pe­cially im­por­tant be­cause the longer you stay up, the more am­phetamines you have to take to stay awake; if your dose gets high enough, and if you’re badly enough sleep de­prived, you put your­self at risk of am­phetamine psy­chosis, which is about as much fun as it sounds like.

There are a num­ber of pre­scrip­tion am­phetamines on the mar­ket, and these are gen­er­ally to be preferred to street speed, due to their pu­rity and lack of adulter­ants. It’s not ter­ribly hard to get di­ag­nosed with ADD/​ADHD, so this can be above-the-board. Dexedrine is pure dex­troam­phetamine, while Ad­der­all is a mix of dex­troam­phetamine and racemic salts (which con­tain a 50%/​50% split be­tween dex­tro- and levoam­phetamine). The differ­ence be­tween the two stereoisomers is com­pli­cated, and your best bet is to ex­per­i­ment to see which works best for you, but a rule of thumb is that Ad­der­all has more “kick” at lower doses, while Dexedrine is stronger at higher doses. Metham­phetamine, you may be sur­prised to learn, is also pre­scribed for ADHD, al­though much more rarely. Meth is stronger, longer-last­ing, and sig­nifi­cantly more ad­dic­tive, than am­phetamine. It is also more neu­ro­toxic. I would recom­mend ex­er­cis­ing ex­treme cau­tion around this one, or else avoid­ing it en­tirely, un­less you ac­tu­ally have se­vere ADHD and this is the only thing that works for you. Lastly, there is a pro­drug for dex­troam­phetamine that just came on the mar­ket, called Vy­vanse (lis­dex­am­phetamine). This has a much slower on­set, since it has to be me­tab­o­lized into dex­troam­phetamine, and there­fore has sig­nifi­cantly less ad­dic­tion po­ten­tial.

Ri­talin works similarly to am­phetamines; ap­par­ently it tends to pro­duce less eu­pho­ria. Ephedrine is chem­i­cally similar to am­phetamines, but works pri­mar­ily by in­creas­ing the ac­tivity of no­ra­drenal­ine; it has the ad­van­tage of be­ing legally available with­out a pre­scrip­tion. I men­tion these only in pass­ing be­cause I don’t have much ex­pe­rience with them; if you want to con­tribute some in­for­ma­tion about them, please com­ment!

I also want to briefly men­tion MDPV (methylene­dioxypy­rovalerone), an ex­per­i­men­tal stim­u­lant still legally available in the U.S. and in Canada (sold on­line as a re­search chem­i­cal or, some­times, as “en­vi­go­rat­ing bath salts”). This one acts as a dopamine and nore­pinephrine re­up­take in­hibitor, pro­duc­ing a state rem­i­nis­cent of that caused by am­phetamines. It has a quick on­set and short life­time (3-5 hours), which makes it well-suited to ac­com­plish­ing quick chores. How­ever, there are a num­ber of nasty side effects re­ported, and it seems to have some ad­dic­tive po­ten­tial. Look­ing at the ev­i­dence, it ap­pears that most of the peo­ple re­port­ing this sort of thing were in­sufflat­ing larger doses; so taken orally and in mod­er­a­tion, this one can still be rea­son­ably safe. But there’s very lit­tle out there that’s peer-re­viewed, so take a look at some trip re­ports and pro­ceed with cau­tion.

All of this prob­a­bly makes it sound like stim­u­lants are, at best, not far off from a zero-sum game: they may benefit cog­ni­tive perfor­mance, but they come with side effects and ad­dic­tive po­ten­tial and a nasty crash when you come off them. Well, good news: we’ll be con­sid­er­ing Modafinil next, which some are call­ing the perfect stim­u­lant. Modafinil is sold by pre­scrip­tion only, but its pro­drug, Adrafinil, can be pur­chased on­line. I’ve taken the lat­ter on a num­ber of oc­ca­sions, and have been quite im­pressed with the re­sults. Adrafinil pro­motes a state of wake­ful­ness and en­ergy, but with­out the “edge” that comes with am­phetamine use. Even un­der con­di­tions of sleep de­pri­va­tion it has a sig­nifi­cant pos­i­tive effect on cog­ni­tive func­tion­ing, mem­ory re­ten­tion, fo­cus and mo­ti­va­tion. It has no sig­nifi­cant crash, pro­duces no tol­er­ance, and seems to have very lit­tle ad­dic­tive po­ten­tial. You can even sleep on Adrafinil, if you wish; this is a sig­nifi­cant ad­van­tage over all of the other stim­u­lants we’ve dis­cussed, since if you take dexedrine at 9PM and finish your work at 1AM, you’re still effec­tively com­mit­ted to stay­ing up all night. Adrafinil also seems to have a pos­i­tive effect on mood; lastly, there are signs it can be used both to pre­vent and to treat some of the effects of ag­ing on en­ergy level and cog­ni­tive abil­ity.

Modafinil and Adrafinil are not perfectly safe, though. They put a fairly heavy load on the liver and kid­neys if taken daily, and should there­fore be taken only oc­ca­sion­ally, un­less as part of med­i­cally-su­per­vised treat­ment. There are also oc­ca­sional side effects to watch out for, most no­tably skin in­fec­tions.

Nootropics

Nootrop­ics are still a very new and ex­per­i­men­tal class of drugs. Many pur­ported nootrop­ics give nega­tive or in­con­clu­sive re­sults in clini­cal tests, and many of them have not been tested at all, or very lit­tle: more speci­fi­cally, most of the re­search has fo­cused around us­ing nootrop­ics to treat neu­ral di­s­or­ders and in­juries, or to miti­gate the effects of ag­ing, with very lit­tle fo­cus on young and healthy in­di­vi­d­u­als. This does not mean, how­ever, that they do noth­ing benefi­cial; it only means that you’ll have to do some care­ful ex­per­i­men­ta­tion to de­ter­mine how they effect you, if at all. For our pur­poses, I’ll only be cov­er­ing some of the more pop­u­lar and (most im­por­tantly) well-stud­ied nootropic drugs.

We’ll start with pirac­etam. The re­search on pirac­etam shows pos­i­tive effects in the pre­ven­tion and treat­ment of apha­sia, de­men­tia, epilepsy and hy­poxic in­jury, but says al­most noth­ing about its effect on healthy in­di­vi­d­u­als. The gen­eral con­sen­sus among those who take it daily is that it seems to do some­thing, though it’s hard to put a finger on. One friend of mine sug­gests that it seems to sub­tly im­prove the gen­eral flow of cog­ni­tion, mak­ing mem­o­ries and good ideas more available. One sig­nifi­cant effect that pirac­etam seems to have is gen­eral po­ten­ti­a­tion of other drugs, es­pe­cially stim­u­lants and psychedelics, so if you in­cor­po­rate pirac­etam into your daily reg­i­men, you should be ex­tra-care­ful about try­ing new drugs.

Another “smart drug” is DHEA, an en­doge­nous chem­i­cal with a va­ri­ety of func­tions, in­clud­ing in­hi­bi­tion of cor­ti­sol. The re­search shows that it has anti-de­pres­sant effects, and seems to im­prove cog­ni­tive func­tion­ing un­der stress­ful con­di­tions. It also seems to im­prove epi­sodic mem­ory in young men, but has no such effect in el­derly peo­ple. You’ll note I said “young men”, not “young peo­ple”: the effects of DHEA ap­pear to be asym­met­ric with re­spect to gen­der. In par­tic­u­lar, higher lev­els of en­doge­nous DHEA are cor­re­lated with longer lifes­pan in men, but there is no such cor­re­la­tion in women.

On the life ex­ten­tion an­gle, an­other nootropic worth con­sid­er­ing is Selegiline, which ap­pears to be available for pur­chase on­line, al­though tech­ni­cally it’s not sup­posed to be sold to any­one with­out a pre­scrip­tion (pos­ses­sion, on the other hand, is le­gal). Selegiline is an MAO-B in­hibitor, com­monly used to treat Park­in­son’s, de­pres­sion and de­men­tia. Even for some­one with­out these con­di­tions, Selegiline pro­duces cog­ni­tive benefits similar to those of Adrafinil, and there are re­ports that long-term use might tend to in­crease your lifes­pan. Look­ing at the ev­i­dence, I am in­clined to take such claims se­ri­ously. Since it tar­gets MAO-B speci­fi­cally, Selegiline is less dan­ger­ous than non­spe­cific MAOIs. How­ever, at higher doses, Selegiline to lose its speci­fic­ity and in­hibit MAO-A also. Women on oral con­tra­cep­tion should be es­pe­cially care­ful, as birth con­trol pills ap­pear to in­crease Selegiline’s bioavaila­bil­ity, so that MAO-A in­hi­bi­tion may kick in at lower doses. At any rate, use cau­tion with this one, and take lower-than-usual doses of other sub­stances, in­clud­ing foods con­tain­ing ty­ro­sine and other po­ten­tially dan­ger­ous monoamines (e.g. choco­late, cheese, wine).

Some other less com­mon nootrop­ics with effects similar to those of the above in­clude Vin­poce­tine and Hy­dergine, which func­tion as neu­ro­pro­tec­tives and might also im­prove cog­ni­tive func­tion­ing. I haven’t tried these, and available re­search is slim, so I can’t say much. Beyond the nootrop­ics we’ve dis­cussed, the field be­gins to look a lit­tle grim. For ex­am­ple, the jury seems to be out on ginkgo biloba: some clini­cal tri­als failed to demon­strate any mea­surable effect on mem­ory or cog­ni­tion, and oth­ers ap­peared to show short-term benefits. It gets worse, though, than merely am­bigu­ous re­search. For ex­am­ple, DMAE, once mar­keted as a life-ex­ten­sion agent, may ac­tu­ally shorten your lifes­pan. Other nootrop­ics have turned out to be severely toxic, such as Fipex­ide, which ap­pears to cause liver failure with pro­longed use. At any rate, your best bet is prob­a­bly to stick with es­tab­lished and well-stud­ied drugs; there are whole com­mu­ni­ties out there perfectly will­ing to put them­selves on the line test­ing new con­tenders, and I feel it’s best to leave that up to them.

Psychedelics and “recre­ational” drugs

Now, says Alice, for psychedelics. We should be­gin with some gen­eral re­marks. First of all, these are con­traindi­cated for any­one with a fam­ily his­tory or pre­dis­po­si­tion to psy­chotic di­s­or­ders. More gen­er­ally, set and set­ting (men­tal state and ex­ter­nal cir­cum­stances, re­spec­tively) are ex­tremely im­por­tant to hav­ing a pos­i­tive ex­pe­rience. Psychedelics have been de­scribed as “non­spe­cific am­plifiers of ex­pe­rience”, which means that if you’re hav­ing a bad day, acid will prob­a­bly make it worse. Ideally, your first trip should be in a place where you feel safe and in­spired, with a few peo­ple you trust and who are ex­pe­rienced and knowl­edge­able about the drug you’re tak­ing. You’ll prob­a­bly want to have art books, sketch­books, good mu­sic and some­place comfy to lie or sit.

Your pro­vi­sos and warn­ings are all well and good, says Bob, but what do psychedelics ac­tu­ally do?

It’s… hard to de­scribe, says Alice, in the same way that the colour red is hard to de­scribe, but I’ll give it a shot; just keep in mind this is an in­com­plete de­scrip­tion. First there are the vi­sual effects. Th­ese aren’t hal­lu­ci­na­tions, in the sense that you’ll rec­og­nize them as be­ing effects of the drug. With your eyes open, you’ll tend to see colours in­ten­sified and al­tered, and your brain will be hav­ing a field day rein­ter­pret­ing in­ter­est­ing tex­tures (cf. parei­do­lia and form con­stants); with your eyes closed, you’ll see an­i­mated ge­o­met­ric pat­terns, tes­sel­la­tions, vi­sions, and all kinds of sur­pris­ingly in­ter­est­ing stuff. Depic­tions in pop­u­lar cul­ture of psychedelic ex­pe­riences are no­to­ri­ously bad, but this movie does a rea­son­ably good job. In ad­di­tion to vi­sual al­ter­a­tions (which can teach you a lot about the func­tion­ing of your vi­sual cor­tex) you might also ex­pe­rience changes in au­di­tory and tac­tile sen­sa­tion, as well as synaes­thetic crossover be­tween senses.

Even more in­ter­est­ing than the sen­sory changes are the cog­ni­tive effects. It turns out that your sense of a co­her­ent self can be over­rid­den, and you may ex­pe­rience a blur­ring of the bound­ary be­tween you and ev­ery­thing else. You may have strange, spon­ta­neous ideas or in­sights; to some ex­tent this is be­cause the pe­cu­liar­ity of the ex­pe­rience forces you to re­ex­am­ine tacit as­sump­tions hid­den deep in your re­al­ity model; these as­sump­tions do not always turn out to be wrong, but it’s good to be aware of them and to un­der­stand them more deeply. You may also be­come un­usu­ally aware of patholo­gies in your lifestyle and re­la­tion­ships, and with prac­tice you may be bet­ter able to ar­tic­u­late those patholo­gies, than you are nor­mally. Ideas that come to you while high must be care­fully ex­am­ined and tested while sober, of course, but my ex­pe­rience has been that many of them turn out to be gen­uinely good ideas, and some have even led to sig­nifi­cant im­prove­ments in my func­tional re­la­tion­ship to the world.

LSD, in par­tic­u­lar, seems well-suited to un­der­stand­ing tech­ni­cal fields, in­clud­ing math and physics. Un­like mush­rooms, acid does not sig­nifi­cantly im­pair my abil­ity to read and un­der­stand math­e­mat­i­cal texts, and the height­ened abil­ity to flex my vi­sual cor­tex al­lows me to see difficult and ab­stract con­struc­tions quite vividly, as well as to un­der­stand on an in­tu­itive level how they work. Mush­rooms, con­versely, are more likely to pre­sent me (some­what force­fully) with ideas I might never have oth­er­wise con­sid­ered. Th­ese two are the most pop­u­lar psychedelics, and the two ex­pe­riences bear a definite fam­ily re­sem­blance. LSD is calmer, and eas­ier to con­trol and di­rect, but it lasts up to twice as long as mush­rooms—twelve hours is com­mon. Mush­rooms tend to be more emo­tion­ally in­tense: usu­ally this means eu­pho­ria and lots of gig­gling, but oc­ca­sion­ally you might be over­come by grief or anger, es­pe­cially if you’re already feel­ing that way be­fore you dose.

I’m not go­ing to say much about cannabis, be­cause while the ex­pe­rience is cer­tainly in­ter­est­ing, it’s prob­a­bly not go­ing to help most of you think bet­ter (there are some, mind you, who ac­tu­ally func­tion bet­ter with THC in their sys­tems; Carl Sa­gan, for ex­am­ple, was a no­to­ri­ous pot­head). One rea­son you might want to take cannabis any­way is that it can serve as a gen­tle in­tro­duc­tion to psychedelia—but be warned that some peo­ple, even those who gen­er­ally en­joy psychedelics, have con­sis­tently bad re­ac­tions to THC. Pro­ceed with cau­tion. Another rea­son to take cannabis is for life ex­ten­sion pur­poses; there’s good ev­i­dence that THC helps pre­vent cer­tain kinds of can­cer. If you’re tak­ing it for health rea­sons, though, you prob­a­bly want to use a vapour­izer or eat it in­stead of smok­ing it. Also note that, at least for some par­tic­u­larly sus­cep­ti­ble peo­ple, cannabis can be ad­dic­tive. Again, if you have rea­son to be­lieve you’re prone to sub­stance abuse, you might want to give this one a skip.

Another con­trol­led sub­stance to con­sider is MDMA. MDMA has a va­ri­ety of neu­ro­chem­i­cal effects: it in­hibits dopamine and nore­pinephrine re­up­take, ac­tu­ally re­verses the sero­tonin re­up­take pump, and also seems to in­crease lev­els of oxy­tocin, the “trust hor­mone”. So, you feel a sense of love, joy, wellbe­ing, safety, etc. You’ll also get many of the same stim­u­lant effects as metham­phetamine, albeit milder. I men­tion MDMA be­cause in my ex­pe­rience, if you already have a de­cent idea of how so­cial in­ter­ac­tions are sup­posed to work but still have trou­ble get­ting over your anx­iety, this can help you teach your­self to be more so­cially con­fi­dent, if taken in the ap­pro­pri­ate en­vi­ron­ment (hint: do this around other peo­ple on MDMA). The surge of oxy­tocin makes you tem­porar­ily fear­less about ap­proach­ing strangers, and also cush­ions the blow if things go badly, while the in­creased dopamine ac­tivity strongly re­in­forces be­havi­ours lead­ing to suc­cess­ful in­ter­ac­tions. This learned con­fi­dence per­sists into the sober state. MDMA is also use­ful for con­fronting emo­tion­ally difficult is­sues—in­deed, it was used for psy­chother­apy be­fore it be­came pop­u­lar recre­ation­ally and was banned—but I’ll leave that to you to re­search on your own.

Some warn­ings about MDMA. First of all, most “Ec­stasy” con­tains adulter­ants (com­monly caf­feine and metham­phetamine and some­times PCP, among oth­ers), and some­times con­tains no MDMA at all. As a gen­eral rule, avoid pressed pills; pure MDMA most com­monly comes in crys­tal form. If you don’t have a re­li­able source, you might want to skip MDMA en­tirely. Also note that MDMA com­monly causes hang­overs, al­though these can be miti­gated by tak­ing 5-HTP.

Lastly, al­though all the drugs I’ve men­tioned in this sec­tion are con­trol­led, you might ac­tu­ally be able to ex­pe­rience very similar al­tered states legally. Alex and Ann Shulgin, the re­search chemist and psy­chother­a­pist (re­spec­tively) who first pop­u­larized MDMA, also came up with liter­ally hun­dreds of other psy­choac­tive com­pounds, many of which are still le­gal out­side Amer­ica and can be pur­chased on­line from so-called “re­search chem­i­cal” com­pa­nies (the U.S. has the Analogues Act, which au­to­mat­i­cally makes ille­gal any chem­i­cal broadly similar to any other ille­gal chem­i­cal, but Canada, among other coun­tries, has not shared this dis­mal fate). For ex­am­ple, in­stead of MDMA, you might con­sider AMT, a tryptamine with similar and in some ways bet­ter effects. Another re­search chem­i­cal, 4-ACO-DMT, is ac­tu­ally me­tab­o­lized into psilocin, as is psilo­cy­bin, and so the trip is al­most iden­ti­cal to that of mush­rooms. The down­side to all this is that re­search chem­i­cals are gen­er­ally sold only in larger quan­tities, so if you don’t want to drop a cou­ple hun­dred dol­lars on some­thing you may not en­joy, this may not be your best bet. There’s also the fact that these are not as well-un­der­stood as more pop­u­lar psychedelics, which makes them riskier, al­though these risks can be min­i­mized by us­ing cau­tion and mod­er­a­tion.

Conclusion

As we’ve seen, says Alice with a smirk, you too can al­ter your neu­ro­chem­istry for fun and profit—but this must be done re­spon­si­bly. Although I’ve tried to give a sense of the dan­gers alongside the benefits, this post is re­ally only meant to serve as a broad in­tro­duc­tion. If you’re think­ing of ac­tu­ally try­ing any of the drugs I’ve men­tioned, it’s im­por­tant that you do some in-depth re­search, and a proper cost-benefit anal­y­sis. But with a lit­tle prac­tice, you too can ex­pand your mind.